There has been a growing interest in recent years in the non-intrusive clinical sampling of body fluids for detecting various chemical and biological substances. This is largely the result of improved analytical techniques and the realization that many of the components of physiological and/or pathological interest (pathogens, biologics, metabolites, drugs, etc.) contained in blood and blood product specimens obtained by intrusive means (e.g., venepuncture) are also contained in other body substances, secretions or fluids such as urine, sweat, tears, respiratory secretions, semen, vomitus, wound and ulcer drainage, or saliva, which can be obtained more easily and at reduced risk. Moreover, even when blood and blood products are used, the amounts of blood required to measure the levels of different components of interest are relatively small compared to the amounts drawn from different people.
In addition, saliva and urine samples may be advantageous for testing of some components of physiological interest. This may be illustrated by comparing the utility of urine and saliva samples to establish recent marijuana usage. Since marijuana can be detected in urine for up to 40 days after the last use of the drugs, while saliva will only show evidence of such usage within the last 48 hours, saliva samples are much more useful than urine samples for detecting recent use of the drug.
Body fluid sampling and testing typically involves four steps: 1) sample Collection 2) extraction of sample from the collection media 3) reaction of the sample with analytical reagents, and 4) detection and/or measurement of physiological or pathological active contents.
In the past, non-intrusive collection of body fluid samples has commonly been accomplished by the use of devices such as cotton swabs, absorbent papers and pads, which are used to absorb fluid samples. Once collected, these devices are placed in a vessel in which the sample is extracted into a suitable solvent by means of diffusion, with or without mechanical agitation. Sample extraction by means of unassisted diffusion is quite slow, usually requiring several minutes. If this process is sped up with agitation, extraneous material such as cotton or paper fibers may be entrained into the extraction fluid along with the sample and may have to be removed prior to the reagent reaction of step 3 above.
Chemical and biochemical analysis of liquids has been traditionally performed in specialized laboratories. The classical methods of analytical chemistry have been increasingly replaced by automated analysis designed for the processing of well-defined specimens. These procedures are typically still conducted in highly specialized institutions by technicians trained in operating particular integrated instruments.
The specimens collected and sent to these specialized clinical testing laboratories for medical diagnosis generally include specimens collected into tubes, vials or containers that hold anywhere from 5 ml to about 20 ml of the liquid sample. Specific amounts, which typically involve only a fraction of the volume collected are used directly or after centrifugation for the measurement of the test ordered. The rest of the specimen is discarded as a biohazard material.
An object of the present invention is to provide a plurality of assemblies for collecting liquid specimens in volumes sufficient to carry out triplicate tests of a specimen and to avoid collection of liquid specimens in excessive amounts, the majority of which is ultimately discarded. Specifically, the basic unit is a one piece barrel container comprising a variety of assemblies of the present invention that are designed to collect liquid specimens for analysis by using open capillary tubes to collect liquid specimens. The basic unit may further include a processing component involving dilution and filteration of the collected sample, and optionally provide an analytical means to analyze and carry out a specific test.
Blood collection for routine clinical testing is generally carried out by venepuncture and varying amounts of blood ranging from 5 ml to 20 ml are collected in vaccutainer tubes having color-coded stoppers. Any disruption of vascular endothelium such as venepuncture during blood collection is a potent stimulus to clot formation. The normal endothelial cell lining of the vessel wall plays an essential role in preventing thrombus formation. The endothelial cells are active metabolically in control of the blood flow, platelet aggregation and the coagulation cascade. Disruption of the endothelial cell surface results in unopposed smooth muscle contraction and vessel spasm. This sets the stage for thrombus formation and makes it difficult to draw blood by venepuncture. In some patients on chemotherapy, drawing blood by venepuncture is virtually impossible; and it makes it difficult to monitor drug levels.
A number of analytic procedures and devices are commonly used to test body fluids for the presence of substances of diagnostic value. Blood and urine are the body fluids most frequently tested. An advantage of blood as a test fluid is that analytes are often at relatively high concentrations and measurement of these concentrations can provide information about a patient's health.
Urine is useful for diagnostic testing when the blood component of interest (e.g., a drug or hormone) is concentrated during urine formation. However, the urine concentration of an analyte does not usually reflect the physiologically active amount of the analyte in the blood.
Not commonly used, but numerous studies have demonstrated that saliva and other types of oral fluid can provide a reliable sample for diagnostic testing involving antibodies or antigens specific for various human or animal pathogens. Oral fluids have also been shown to be useful in measuring the body levels of naturally occurring hormones or therapeutic and other drugs. A trained phlebotomist is not required as is the case with blood, nor are special arrangements for privacy-in-collection and custody of the sample required, as is the case with urine. Collection of an oral fluid sample obviates the hazard of handling blood-contaminated needles and tubes.
Virtually all samples for analysis of blood cells of their constituents such as hemoglobin, are collected into tubes containing potassium or sodium salts of elhylenediamine tetra acetic acid (EDTA). EDTA, an avid calcium chelator, serves as an effective anti-coagulant that inhibits activation of the coagulation system and production of fibrin clots. Samples with clots are not suitable for analysis of fluid components. Heparin can be used as an anticoagulant without introducing a dilution error but unfortunately, it causes platelet and leukocyte agglutination, which interferes with accurate cell enumeration. For these reasons, citrate and heparin are not routinely used for blood sample collection.
The field of competitive protein binding assays or specific binding assays has greatly expanded, as its importance in the diagnostic field has become recognized. The ability to be able to detect a specific compound and measure the compound quantitatively has permitted the monitoring of the administration of a wide variety of drugs, the determination of an imbalance in a wide variety of hormones, the quantification of physiologically active proteins, and the diagnosis of diseases through detection of a pathogen. The different techniques have been distinguished in requiring or not requiring separation steps, the nature of the signal developed by the label, the development of the signal in a solution or on a surface and the manner of the measurement for a quantitative determination. The various biochemical and immunologic procedures are set forth in scientific literature and in U.S. Pat. Nos. 4,900,663; 4,999,285; 5,030,558; 5,039,607; and 5,935,864.
U.S. Pat. No. 5,935,864 ('864 patent) describes a self contained unit for collecting and analyzing samples of liquid specimen including a specimen container having an open capillary end and an open top with a chamber disposed there between, the chamber including a means therein for analytical testing, and, a vial having a sealed top end, the top end being of pre-selected size to receive the lower end of the sample container in a substantially air tight arrangement upon being penetrated by the capillary end. This reference is incorporated in its entirety herein. However, the self-contained unit described, has several disadvantages. Since the capillary end does not have a coating of an anticoagulant, it is a disadvantage because once the sample is drawn into the capillary end, the operator or technician has to move with speed to carry out the analysis otherwise the blood will clot in the capillary tip.
Another disadvantage of the unit described is that there is no means of filtering the sample before it is contacted with the test strip, and therefore the sample may contain contaminants and particulate matter that may interfere with the analysis of the test component.
Yet an additional disadvantage of the unit described is the lack of a support cap for the test strip at the open end of the container, thereby not allowing the inversion of the tube to allow the sample to travel along the test strip not only by absorption but also by gravity.
An additional disadvantage of the unit described in the '864 patent is that it provides no graduated means of measuring the volume of the sample collected.
The above disadvantages have been overcome in the present invention.